N-Terminal Pro-B-Type Natriuretic Peptide (NT-proBNP)—A Prognostic Biomarker in Older and/or Frail Adults with Advanced Gastroesophageal Cancer: A Post Hoc Analysis of the GO2 Clinical Trial
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Dundee Medical School, Ninewells School of Medicine, University of Dundee, Dundee DD1 9SY, UK
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Department of Cardiology, Ninewells Hospital, Dundee DD1 9SY, UK
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Division of Cardiovascular Research, Ninewells School of Medicine, University of Dundee, Dundee DD1 9SY, UK
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Division of Cancer Research, Ninewells School of Medicine, University of Dundee, Dundee DD1 9SY, UK
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Tayside Cancer Centre, Ninewells Hospital, Dundee DD1 9SY, UK
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Edinburgh Cancer Research Centre, University of Edinburgh, Edinburgh EH8 9YL, UK
*
Author to whom correspondence should be addressed.
Cancers 2025, 17(4), 601; https://doi.org/10.3390/cancers17040601
Submission received: 9 January 2025
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Revised: 3 February 2025
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Accepted: 9 February 2025
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Published: 10 February 2025
(This article belongs to the Special Issue Oncology: State-of-the-Art Research in UK, 2nd Edition)
Simple Summary
Aging is associated with increasing comorbidity and frailty, all of which are associated with poorer cancer outcomes. Older adults with cancer are often excluded from clinical trials; therefore, we lack data to inform our decision-making appropriately. This is particularly relevant in poor prognosis cancers such as those of the upper intestinal tract. The identification of novel prognostic biomarkers may help personalise management plans. One such potential biomarker is serum N-terminal pro-B-type Natriuretic Peptide (NT-proBNP). Serum NT-proBNP can be used as a measure of cardiac health and function and has established links with sarcopenia, which is prognostic in cancer. We therefore aimed to investigate the role of NT-proBNP as a prognostic biomarker in advanced gastroesophageal cancer using the data from a completed clinical trial in older and/or frail patients (the GO2 trial). The GO2 trial investigated the role of chemotherapy dose de-escalation in older and/or frail patients. Our results demonstrate an association between pre-treatment levels of NT-proBNP (cBNP) and overall survival; those with higher levels had poorer survival. We also found that there was no clear association between age, patient fitness and NT-proBNP. These findings suggest that NTproBNP may warrant further investigation as a prognostic biomarker and as an adjunct to decision-making in clinics.
Abstract
Background: Better prognostic biomarkers are needed in older adults with cancer. There are established links between N-terminal pro-B-type Natriuretic Peptide (NT-proBNP) and sarcopenia, and sarcopenia is associated with poorer cancer survival. However, there are limited data regarding baseline NT-proBNP as a biomarker of cancer outcome. The GO2 trial recruited older and/or frail United Kingdom (UK) patients with advanced gastroesophageal cancer and investigated the role of chemotherapy dose de-escalation. Using the GO2 database, we sought to investigate the prognostic role of NT-proBNP as well as the interaction between NT-proBNP and frailty. Methods: This was a post-hoc analysis of a completed clinical trial. Frailty measures included ECOG performance status (PS) and GO2 frailty grouping (based on an assessment of nine geriatric domains). A corrected NT-proBNP (cBNP) was calculated for each patient, adjusting for the upper limit of normal (ULN) reference from each centre. Results: A total of 241 patients were eligible to be included in the analysis. The median age was 76 (range 52–89), 187 (77.6%) were male and 211 (87.6%) had adenocarcinoma. Eighty (33.2%) patients had a baseline NT-proBNP above the local ULN. There was no association between cBNP and ECOG PS (p = 0.36) or the GO2 frailty group (p = 0.58). Those with the highest cBNP (n = 59) had significantly inferior median overall survival: 5.3 months (mos.) vs. 6.8 mos. (medium, n = 120) vs. 8.2 mos. (low, n = 61); HR 1.57 (95% CI; 1.04–2.37), p = 0.031. This was maintained on a Cox regression analysis (HR 1.69, p = 0.01) accounting for the GO2 trial stratification factors. There was no clear association between frailty and NT-proBNP. Conclusions: In this study, NT-proBNP appeared to be prognostic-independent of other factors. Further investigation and validation are needed to confirm our findings and to determine the potential beneficial role of cardioprotective therapy in at-risk patients with cancer identified in this manner.
Keywords:
gastroesophageal cancer; frailty; geriatric oncology; sarcopenia; biomarkers
